Compounds of formula I are described in WO 01/97786:
wherein    R1, R2 and R3 are independently from each other hydrogen, lower alkyl, lower alkoxy or halogen;    R4 is hydrogen, lower alkyl, lower alkyloxy, halogen,            or is a five or six membered non aromatic heterocyclyl group, unsubstituted or substituted by lower alkyl or an oxo-group, or is        —NR5R6, wherein R5 and R5 are independently from each other hydrogen, lower alkyl, —C(O)-lower alkyl, —(CH2)nO-lower alkyl or benzyl, optionally substituted by lower alkyl, or is a five or six membered heteroaryl group;            R1 and R2 or R2 and R3 may form together with the corresponding carbon atoms a ring containing —O—CH2—O— or —CH═CH—CH═CH—;    R is hydrogen or —C(O)R′;    R′ is a five or six membered non aromatic heterocyclyl group, five or six membered heteroaryl group or is aryl, which rings may be substituted by the groups, selected from lower alkyl, halogen-lower alkyl, lower alkoxy, cyano, nitro, —C(O)H, —C(O)OH or by pyrrolidin-1-yl-methyl;    n is 1 to 4;or a pharmaceutically acceptable salt thereof.
In particular, WO 01/97786 describes compounds of formulas IA and IB

Compounds of formula IA may be used as intermediates for the preparation of compounds of formula IB, which compounds are pharmaceutically active as adenosine receptor ligands.
Compounds of formula IB are important in the regulation of many aspects of cellular metabolism and in the modulation of different central nervous system activities. As such, the compounds of formula IB may be used in the control or prevention of illnesses based on the modulation of the adenosine system, such as Alzheimer's disease, Parkinson's disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, asthma, allergic responses, hypoxia, ischaemia, seizure and substance abuse. Furthermore, compounds of the present invention may be useful as sedatives, muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardioprotective agents. The most preferred indications for compounds of formula IB are those, which are based on the A2A receptor antagonistic activity and which include disorders of the central nervous system, for example the treatment or prevention of certain depressive disorders, neuroprotection and Parkinson's disease. The compounds are further useful in the treatment of diabetes mellitus, obesity and ADHD (attention deficit hyperactivity disorder).
In general, the preparation of compounds of formula I, wherein R is hydrogen, is well known. For example, in WO 01/97786 the following process is described:
wherein the numbers 1–4 have the following meaning:                1 HR4, Pd(OAc)2, BDCP, K3PO4, DME (ethylene glycol dimethl ether), 80° C./24 h/90%;        2 H2, Pd—C, EtOH/CH2Cl2, RT/12 h/95%;        3 PhCONCS, acetone, RT/30 min/95% and NaOMe, MeOH, RT/2 h/90%;        4 SOCl2, 55° C./10 min/75%;BDCP is        

The definition of substituents is described above.
It has been shown that most of the starting materials and the ligand are very expensive and only available in small quantities, and the cyclization step could not be scaled up without resorting to chromatography.
Another way to produce amino-benzothiazoles is described in EP 282971 as follows:

It has been shown that this reaction step often leads to amino-benzothiazoles in low yields due to competing reactions.
EP 529 600 describes a process for preparation of amino-benzothiazoles comprising the following step:

It has been shown that the reaction variants, conducted according to literature precedent, such as Br2/CHCl3 or AcOH, I2/MeOH or SOCl2/CHCl3 are often not suitable for the preparation of amino-benzothiazoles, especially in large amounts.
Due to the relative high electron density within the amino-substituted phenyl ring in some specific cases required for the present purposes, competing reactions on this ring before or after cydization always occurred to a certain extents. Other approaches such as the use of aq NH4Br and H2SO4 (EP 529600) or treating the aniline directly with NaSCN/Br2/AcOH (Synthesis, 970, 31, 2000) failed to offer any improvement.
A more subtle way of activating the thione sulphur atom was found in the acid catalyzed transfer oxidation of thioureas with DMSO (J. Heterocyclic Chem., 63, 37, 2000). But in the absence of suitable trapping agents a dimerization reaction took place to give undesired iminothiadiazoles.
All methods, described in the literature, do not give the desired end products of formula IA and IB in good yields without unpredictable side products.